T-Cells and B-Cells Flashcards
What are the 3 types of αβT Lymphocytes
CD4+
CD8+
Regulatory (Express CD3+,CD4+ and CD25+)
CD4+ T-cells are also known as ___________
Helper T-Cells
CD8+ T-cells are also known as ___________
Cytotoxic T-Cells
MHC class 2 presents peptides to the ____ T-cells
CD4+ (Helper T-cells)
MHC class 1 present peptide to the ____ T-cells
CD8+ (Cytotoxic T-cells)
All T-cells express_____
CD3+
The thymus is a _______ lymphoid organ located in the __________________
Primary
Anterior Mediastinum
The thymus consists of __ lobes surrounded by a _____________. Each lobe further subdivides into lobules that are separated by ______________ called ______ or ________
2 lobes Fibrous Capsule Fibrous connective tissue Septa Trabeculae
The cortex of the Thymus contains a _______________________________
A dense collection of immature T-cells
The medulla of the Thymus is ___________________
Sparsely filled with slightly matured T-cells
A developing T-cells is called a _________
Thymocyte
Lymphoid progenitors don’t express ___, ___ or the _____ migrates to the thymus in the ____ week of gestation
Don’t express CD4, CD8 or the T-Cell Receptor (TCR)
7/8th week of gestation
The T-cell precursors spend about _________ in the ______
3 weeks
Thymus
Explain the development of the T-cells in the Thymus
- T-cell precursors enter the thymus via the cortex and begin to proliferate (Don’t express CD4/8 .’. called Double Negative DN cells)
- β-chains are rearranged, every chain is different meaning we can respond to many different antigens
- CD4 and CD8 are now expressed (Called Double Positive DP cells)
- Chemokine CCR7 receptor is expressed which guides DP cells to the medulla
- The Thymocytes begin to proliferate like crazy (Important step in maturation)
- After proliferation, α chain rearrangement occurs
Explain how β chains are rearranged
- D to J rearrangement
- Part of the J region of the DNA is excised and the remaining region is spliced with the D region becoming a D-J region
- Excised region forms a TREC (T-cell Receptor Excision Circle) - V to D-J rearrangement
- Part of the V region is excised and the remaining region is spliced with the D-J region
- Excised region forms a TREC - Region of DNA created is expressed and becomes the β chain
Explain how α chains are rearranged
An are between the V and J regions is excised and we get V and J being spliced together
A Signal Joint TREC, sjTREC, is formed
__% of thymocytes do not mature and instead become ________ due to the absence of a productive ___ or failure to survive selection
98%
Apoptotic
TCR
Explain the process of Positive Thymocyte selection:
- Thymocyte must bind to a self MHC molecule, if not it will become apoptotic
- If the thymocyte binds to MHC class 1 it will be using it’s CD8+ marker and it will lose the CD4+ marker to become a Cytotoxic T-Cell
- If the thymocyte binds to MHC class 2 it will be using its CD4+ and it will lose the CD8+ marker to become a Helper T-Cell
If the thymocyte cannot bind to an MHC molecule, or has a ____________ selection, it will become _________
Lack of positive selection
Apoptotic
If the thymocyte binds too strong to the ___ or a __________ it is potentially ________ and will become _________. This is called ________ selection
MHC or a self antigen
Dangerous
Apoptotic
Negative
Thymocytes that survive the selection process are known as ____________________ and they will migrate into the _________________ as ______________ T-cells
Immature Single Positive Thymocytes
Circulatory system
Mature but naive T-cells
Regulatory T-cells are T-cells that _________________. They express ____
Recognise Self-Antigen
CD25+
Regulatory T-cells scan the periphery for ____________, and ensure that there is minimal ________.
Self-reactive T-cells
Damage
The Thymus ________ with age, every year after the 1st year functional thymic tissue is replaced by ________
Involutes
Adipose
After primary antigen exposure some T-cells differentiate to form __________
Memory T-cells
When memory T-cells are exposed to antigen again what happens?
They rapidly differentiate into effector T-cells specific to that antigen. This speeds up the secondary response
CD4+ T-cells can be categorised in 3 groups depending on their function, what are they?
T-Helper 1 cells (TH1)
T-Helper 2 cells (TH2)
T-Helper 17 cells
TH1 cells have roles in defense against __________________. They do this by……
- Intracellular microbes
- Activating Macrophages, via Interferon-γ (IFN-γ), to ingest and destroy internalised microbes
TH2 cells have roles in defense against ___________________. They do this by……
- Helminthic parasites
- Stimulating reactions that eradicate Helminithic parasites by releasing interleukins
- IL-4 induces the antibody response
- IL-5 activates Eosinophils
TH17 cells have roles in defense against _______________________. They do this by…..
- Extracellular bacteria and fungi
- Secreting cytokines that attract neutrophils to the site of infection by releasing Interleukins
- IL-17 recruits neutrophils
- IL-22 maintains epithelial integrity so it remains like a barrier
CD8+ T-cells attach to infected cells via MHC class _. When bound they release ______ which breaks down the cell membrane and ______ which causes apoptosis
2
Perforin
Granzyme
How do B-cells recognise antigen?
They can either recognise it directly on the pathogen or have it presented to them by an Antigen Presenting Cell (APC)
Antigens have to be capture and transport to the ____________ of the ___________________ where they can be recognised
B-Cell areas
Peripheral Lymphoid organs
Complement Receptor activation _________ the B-cells response to an antigen bound to it
Increase
What happens when a B-Cell recognises antigen?
It will differentiate into a plasma cell that produces antibodies of the same specificity for the antigen recognised
Antibody molecule, aka _____________, can be ___________ or _________ and are comprised of a _______ and _______ chain.
Immunoglobulins
Membrane-Bound or Secreted
Heavy and Light chain
If B-cells have never encountered antigen before they will express ____ on their cell surface.
IgM
Antibodies can be divided into __________. They have __________ functions in _________ places
Isotypes
Different functions in different places
The function of an antibody is determined by the ___________, it determines the formation of _______ or _______ due to the way their __ regions bind.
Heavy Chain
Dimers or Pentamers
FC regions
___________ affect antigen specificity
Light chains
Explain the development of B-Cells
- Cells committed to the B-cell lineage start to mature in the bone marrow and foetal liver
- Immature B-cells migrate from the bone marrow to peripheral lymphoid organs, particularly the spleen
- Maturation completes in the peripheral lymphoid organs
- Naive B-cells (expressing IgM +/- IgD) then enter the bloodstream and populate the peripheral lymphoid organs
Briefly describe the spleen:
- Located in the upper quadrant of the abdomen
- Fist shaped and weighs 150g
- Encapsulated and Highly vascularised
- Comprised of red and white pulp separated by the marginal zone
What occurs in the Red pulp of the spleen?
- Filtration of the blood
- Full of macrophages that remove microbes, damaged cells and antibody coated antibodies from the blood
What occurs in the White pulp of the spleen?
- Promotion of adaptive responses to blood borne antigen
- Densely packed with lymphocytes to carry out this task
B-cells and T-cells __________ interact with each other, so in the spleen and other lymphoid organs we get ________________________________________
Don’t like to
Segregation into the B-cell and T-cell zones
The heavy chain of Ig’s is encoded by the _______ gene segments
V, D and J
The light chain of Ig’s is encoded by the _______ gene segments
V and J
Summarise Ig Chain rearrangment:
- Heavy chain rearranges first
- Successful rearrangement results in heavy chain being expressed on the cell surface and signals for survival
- The κ locus of the light chain will attempt to rearrange
- If κ locus fails to productively rearrange then the λ locus will rearrange to complete the IgM molecule
- Once the cell expresses IgM it is known as an immature B-cell
Describe the B-Cell selection processes:
Positive Selection - If the B-Cell expresses IgM then it is positively selected
Negative Selection - They get a second chance to express IgM but if they don’t or if they are self reactive they are removed. This is called receptor editing
Explain the Humoral Response:
- B-cell is activated by antigen and T-helper cells
- B-cell clones and then differentiate into plasma cells
- Plasma cells secrete IgM, If a different antibody is needed then plasma cells can undergo Isotype switching, changes it’s receptor
- Receptors can mature over time to increase affinty for the antigen (called Affinity Maturation)
- Some B-cells become memory B-cells
The _______________ of memory B-Cells for antigen is what makes subsequent immune responses _______.
Increased affinty
Faster
B-2 B-cells are formed in the _________ and mature in the _________. They can be classed as _______________________ or _______________________.
Bone Marrow
Spleen/Other Lymphoid tissue
Marginal Zone B-2 B-cells
Follicular Zone B-2 B-cells
What are Follicular Zone B-2 B-cells?
- Found in the white pulp (lymphoid follicles)
- Express IgM and IgD when they are naïve
- Wait in the follicles until they are exposed to antigen
What are Marginal Zone B-2 B-cells?
- Found in the marginal zone of the spleen (area between the red and white pulp)
- Express complement receptors and IgM
- Less diverse
T-dependent antigens _________ Helper T-cells to activate a _______________. They are usually __________ and _________________ are involved in the response.
Require
Humoral response
Proteins
Follicular B cells
T-independent antigens __________ Helper T-cells to activate a _______________. They are usually __________, ________ or ___________ and _________________ are involved in the response.
Don’t require
Humoral response
Polysaccharides, some Lipids, Nucleic acids
Marginal B-cells
_____ helps a T-cell stay in the ________, in order to move to it’s B-cell partner, the T-cell must _____ regulate CCR7 and ______ regulate CXCR5
CCR7
T-cell zone
Down regulate
Up regulate
______ helps attract the T-cell to CXCl13 which is produced by __________ in the B-cell zone
CXCR5
Dendritic cells
B-cells will up regulate _____ which allows it to move towards the T-cell zone by being attracted to the ______ and ______ that are produced by the antigen presenting cells that presented to the T-cells
CCR7
CCL19
CCL21
Different antigens will make T-cells produce different __________ to help the B-cells _______________________________________.
Cytokines
Make the most appropriate immune response
___ receptors recognise the ___ region and bind it to antibody which promotes phagocytosis of __ coated microbes
FC
FC
Ig
